{
  "abstract": "Circulating tumor cells (CTCs) are clinically relevant markers of metastasis and prognosis in gastrointestinal (GI) cancers. However, their extreme rarity and the limitations of current in vivo models severely restrict mechanistic studies of tumor cell dissemination. Here, we demonstrate for the first time that the avian chorioallantoic membrane (CAM) assay can serve as a biologically relevant and ethically advantageous 3R‐compliant (Replacement, Reduction, and Refinement) in vivo model for investigating spontaneous CTC generation. Six green fluorescent protein (GFP)‐labeled human colorectal, pancreatic, and cholangiocarcinoma cell lines were xenografted onto the CAM. Using a standardized workflow, we achieved reliable detection and isolation of GFP‐positive single CTCs from small‐volume CAM blood samples. Critically, we reproducibly confirmed the presence of spontaneously shed CAM‐derived CTCs independent of GFP expression using three established, clinically relevant CTC detection platforms. Subsequent single‐cell whole‐genome amplification enabled downstream short‐tandem repeat (STR) profiling to authenticate CTC identity, alongside detection of tumor‐specific point mutations and copy number alterations (CNAs). Isolated CTCs exhibited high genetic concordance with their parental cell lines, validating the technical robustness of our workflow and establishing the CAM assay as a versatile, scalable platform for investigating hematogenous dissemination and CTC biology outside of mammalian models. Consequently, the CAM assay opens new avenues for early mechanistic and pharmacological CTC research, including functional studies of patient‐derived material.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Surgery (A) Heinrich‐Heine‐University and University Hospital Duesseldorf Germany",
    "Liquid Biopsy Center Duesseldorf Center for Integrated Oncology Aachen Bonn, Cologne Germany",
    "VyCAP B.V Enschede The Netherlands",
    "Department of Obstetrics and Gynecology University Hospital and Medical Faculty of the Heinrich‐Heine‐University Duesseldorf Germany",
    "Department of Gastroenterology, Hepatology and Infectious Diseases University Hospital Duesseldorf, Medical Faculty of Heinrich Heine University Duesseldorf Germany",
    "JCCU Translational Surgical Oncology (A430) German Cancer Research Center (DKFZ) Heidelberg Germany",
    "DKFZ‐Hector Cancer Institute, Medical Faculty Mannheim Heidelberg University Mannheim Germany",
    "Department of Surgery Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University Mannheim",
    "Department of General, Visceral, Vascular and Transplantation Surgery University Hospital Essen Germany"
  ],
  "article_type": "brief report",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Dennis Roth",
      "orcid": "0000-0002-7044-8543"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rui P. L. Neves",
      "orcid": "0000-0002-4515-739X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Julia Geheb"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Christian Ballmeyer"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nathalie Gaßmann"
    },
    {
      "affs": [
        2
      ],
      "name": "Kiki C. Andree"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Monica Sudarsanam"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Christiane Driemel"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Celine Örencik"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Andrè Franken"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Eslam Elmaghraby"
    },
    {
      "affs": [
        4
      ],
      "name": "Sven H. Loosen"
    },
    {
      "affs": [
        4
      ],
      "name": "Roderburg Christoph"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Sebastian Schoelch"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Hans Neubauer"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wolfram T. Knoefel"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nikolas H. Stoecklein",
      "orcid": "0000-0002-3412-594X"
    },
    {
      "affs": [
        0,
        1,
        8
      ],
      "name": "Georg Fluegen",
      "orcid": "0000-0002-9322-1659"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bzpqf2s6k1kbf.bib",
  "cited_by": 0,
  "doi": "10.1002/1878-0261.70336",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13587589/",
  "id": "bzpqf2s6k1kbf",
  "issns": [
    "1574-7891",
    "1878-0261"
  ],
  "landing_url": "https://doi.org/10.1002/1878-0261.70336",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Liquid Biopsies"
    ],
    [
      "heading",
      "Metastasis"
    ],
    [
      "heading",
      "Model Organisms"
    ],
    [
      "heading",
      "Short Report"
    ],
    [
      "openalex",
      "2730|Cancer Cells and Metastasis"
    ]
  ],
  "openalex": "W7213557534",
  "pdf_url": null,
  "pmcid": "PMC13587589",
  "pmid": "42757743",
  "published": "2026-09-18",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/bzpqf2s6k1kbf.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:23:30Z",
      "native_id": "PMC13587589",
      "source": "pmc",
      "url": "https://doi.org/10.1002/1878-0261.70336"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Cells and Metastasis",
      "subfield": "oncology"
    }
  ],
  "title": "Bridging the gap: a genetically validated avian chorioallantoic membrane platform for investigation of spontaneous circulating tumor cells",
  "title_text": "Bridging the gap: a genetically validated avian chorioallantoic membrane platform for investigation of spontaneous circulating tumor cells",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:20:58Z",
  "url": "https://research.draconitic.com/paper/bzpqf2s6k1kbf",
  "venue": "Molecular Oncology",
  "versions": []
}